Acute adenovirus infections of the eye and respiratory tract continue to be a significant health problem for both immunocompromised and normal individuals. This is due in part to an incomplete understanding of how the virus invades host cells following association with specific receptors (CAR and ?v integrins). In this R21 application, scientists with expertise in biophysical methods and basic molecular virology will team up to unravel the complex process of capsid disassembly that ensues from receptor binding. These studies could provide a guide for investigating how other viruses undergo conformational changes during cell infection and may open up an avenue for designing new antiviral agents to hinder virus host cell entry.